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Metabolic syndrome is associated with mortality in elderly patients with acute respiratory distress syndrome

Diabetology & Metabolic Syndrome volume 16, Article number: 191 (2024) Cite this article

Abstract

Background

This study aims to evaluate the association of metabolic syndrome (MetS) with the risk of all-cause mortality in elderly patients with acute respiratory distress syndrome (ARDS).

Methods

Elderly ARDS patients (≥ 65 years) enrolled from our hospital between January 2018 and July 2023 were divided into the MetS group or the non-MetS group. The outcomes were 28-day and 90-day all-cause mortality rates in the total population and two subgroups stratified by age (65–75 years and ≥ 75 years). Multivariate Cox regression was employed to assess the association of MetS with all-cause mortality, after controlling for potential cofounding factors.

Results

A total of 946 patients were divided into the MetS group (n = 410) or the non-MetS group (n = 536). The 28-day and 90-day all-cause mortality rates were significantly higher for MetS group compared to non-MetS group in the total population and two subgroups (all P < 0.01). Multivariate Cox regression indicated that MetS was significantly associated with a higher risk of 90-day all-cause mortality in the total population (HR = 1.62, 95% CI: 1.22–2.15; P < 0.01), and subgroups of patients aged 65–75 years (HR = 1.52, 95% CI: 1.04–2.21; P = 0.03) and ≥ 75 years (HR = 1.90, 95% CI: 1.23–2.94; P < 0.01). Moreover, with each MetS criterion added from 0 to 1 to 2, 3, and 4 of 4 criteria, both 28-day and 90-day all-cause mortality rates significantly increased (both P < 0.01).

Conclusion

MetS was associated with higher risks of 28-day and 90-day all-cause mortality in elderly patients with ARDS.

Background

Acute respiratory distress syndrome (ARDS) is an acute, diffuse, and inflammatory form of lung injury, characterized by non-cardiogenic pulmonary edema and refractory hypoxemia [1, 2]. A global observational study indicated that the prevalence of ARDS during intensive care unit (ICU) admission was 10.4% and the hospital mortalities reached to 34.9%, 40.3% and 46.1% for those with mild, moderate, and severe ARDS, respectively [3]. Although ARDS can affect people of all ages, increasing age is a widely reported risk factor and is associated with increased mortality in ARDS patients [4]. Thus, early prognostic predictors of ARDS in elderly population have always been a topic under exploration.

Metabolic syndrome (MetS) is a worldwide pandemic and complex disorder, defined as a combination of interconnected factors which caused metabolic, anthropometric, and hemodynamic abnormalities [5, 6]. According to China Health and Retirement Longitudinal Study (CHARLS), the overall prevalence of MetS increased with age augments, ranging from 30.93% for participants aged 40–50 to 35.78% for those aged 60–70 [7]. MetS patients suffered 2.21 times of cardiovascular mortality and propensity to various types of cancers [8, 9], adding substantial burden to patients and their households. Although MetS-related comorbidities including obesity and diabetes have been individually studies in ARDS, the association between overall poor metabolic heath and prognosis of ARDS was rarely reported especially in elderly population.

The present study aims to evaluate the association of MetS with all-cause mortality in elderly patients with ARDS.

Methods

Patients

This is a retrospective study conducted on consecutive patients with ARDS admitted into Shanghai Construction Group Hospital between January 2018 and July 2023. Shanghai Construction Group Hospital is a secondary general hospital with approximately 30 departments and more than 400 beds. Patients aged 65 years and above with an established diagnosis of ARDS were included. The diagnosis of ARDS was made by clinicians according to the Berlin ARDS definition [10] as follows: [1] acute onset; [2] oxygenation index (PaO2/FiO2) ≤ 200 mmHg (1 mmHg = 0.133 kPa) and positive end-expiratory pressure ventilation ≥ 5 cm H2O (1 cmH2O = 0.098 kPa); [3] orthopantomogram showing bilateral pulmonary infiltrates; [4] source of pulmonary edema, that is, a respiratory failure that cannot be explained by cardiac insufficiency or fluid overload; and [5] no other physiological disturbances. Patients were excluded if they any malignancy or incomplete follow-up data.

Data collection and outcomes

Patients were divided into MetS group or non-MetS group based on the modified version of National Cholesterol Education Program (NCEP), Adult Treatment Panel III (2001) [11]. The definition of MetS status requires the presence of any three or more of the following criteria: [1] systolic blood pressure ≥ 130 mm Hg and/or diastolic blood pressure ≥ 85 mm Hg or diagnosed hypertension on treatment; [2] serum TG ≥ 1.7 mmol/L; [3] serum high-density lipoprotein-cholesterol < 1 mmol/L in male, or < 1.3 mmol/L in female; [4] fasting blood glucose ≥ 5.6 mmol/L or diagnosed diabetes on treatment; [5] body mass index (BMI) > 25 kg/m2 for Asians. Since our medical record lacks waist circumference measures, BMI was utilized as a surrogate to depict the abdominal obesity. Baseline patients’ characteristics including age, sex, BMI, smoking habit, primary etiology, and comorbidities were recorded. The International Classification of Diseases (ICD)-10 diagnostic codes were J80 for ARDS, R73 for prediabetes; E10-E14 for diabetes; E66 for obesity; I10 for hypertension; E78 for dyslipidemia; J12-J18 for pneumonia; A40-A41, R57.2 and R65.1 for sepsis; J69.0 for aspiration; S00-S99 and T00-T98 for trauma; Z51.3 for transfusion; K00-K93 for hepatic/gastrointestinal diseases; D80-D89 for immunocompromised diseases; J44 for chronic obstructive pulmonary disease; and N00-N99 for renal diseases.

The primary outcomes include 28-day and 90-day all-cause mortality rates in the total population. The secondary outcomes were 28-day and 90-day all-cause mortality rates in two subgroups aged 65–75 years and ≥ 75 years. The number of days to death counted started on the date of diagnosis of ARDS. The primary outcomes were set in line with several previous studies [1, 12, 13].

Statistical analysis

Statistical power was determined on the primary outcome of 90-day mortality. It was determined that 410 patients in each group could provide a power of > 90% with an alpha of 5% to determine a difference of 10% in the incidence of 90-day all-cause mortality.

All categorical variables were summarized as counts and percentages. The differences in primary and secondary outcomes (28-day and 90-day all-cause mortality rates) and other categorical variables between MetS group and non-MetS group or among groups with different numbers of MetS criteria were analyzed by chi-square tests or by Fisher’s exact tests as appropriate. Continuous variables with normal distributions were presented as mean ± standard deviation (SD) and compared with the use of student’s t-test, and those with non-normal distributions were presented as median (interquartile range [IQR]) and compared with Mann-Whitney U tests.

Participants who were still alive at the end of their last follow-up were censored. A log-rank test was used to test differences in time to all-cause mortality between two groups which were graphically presented by Kaplan-Meier curves. Multivariate Cox regression analysis was used to evaluate the predicting value of MetS status for all-cause mortality, after controlling for potential cofounding factors. All tests were 2-sided and a P value of less than 0.05 was considered significant.

All statistical analyses were performed with the SPSS statistical software program package (SPSS version 22.0 for Windows, Armonk, NY: IBM Corp.).

Results

Figure 1 displayed the flowchart of study population selection. From January 2018 to July 2023, a total of 1,211 elderly patients ≥ 65 years were hospitalized with ARDS. After excluding 265 patients due to incomplete follow-up data or malignancy, 946 patients were enrolled in this study and divided into MetS group (n = 410) or non-MetS group (n = 536). Baseline characteristics of the total population and its two subgroups (65–75 years and ≥ 75 years) are provided in Table 1. In the total population and two subgroups stratified by age, compared to patients without MetS, patients with MetS had higher proportions of smokers, prediabetes or diabetes, obesity, hypertension, and dyslipidemia (all P < 0.01). In addition, the BMI, Acute Physiology And Chronic Health Evaluation (APACHE) II score and Sequential Organ Failure Assessment (SOFA) score in the MetS group were significantly higher than those in the non-MetS group (all P < 0.01). The differences in the age, primary ARDS etiology, ICU length, and most comorbidities were not statistically significant between MetS and non-MetS groups (all P > 0.05).

Fig. 1
figure 1

The flowchart of study population selection

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Table 1 Baseline characteristics of the study population
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In the total population, the 28-day (27.3% vs. 17.4%, P < 0.01) and 90-day (32.9% vs. 21.8%, P < 0.01) all-cause mortality rates were significantly higher for patients with MetS compared to those without MetS. In two subgroups, differences in the 28-day and 90-day all-cause mortality were also significant between MetS and non-MetS groups (all P < 0.01). As shown in Fig. 2, the Kaplan-Meier survival curve displayed that compared with those without MetS, the risk of all-cause mortality was significantly higher (all P < 0.01) in patients with MetS in the total population (Fig. 2A) and two subgroups (Fig. 2B).

Fig. 2
figure 2

Kaplan-Meier survival functions between metabolic syndrome (MetS) group versus non-MetS group of 90-day all-cause mortality in (A) the total population and (B) subgroups stratified by age

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Multivariate Cox proportional hazards regression analysis was performed to explore prognostic factors associated with the risk of all-cause mortality (Table 2). It is shown that after adjusting for potential confounding factors, MetS (HR = 1.62, 95% CI: 1.22–2.15; P < 0.01), age ≥ 75 years (HR = 1.41, 95% CI: 1.10–1.81; P < 0.01), higher APACHE II scores (HR = 1.16, 95% CI: 1.05–1.49; P = 0.03) and higher SOFA scores (HR = 1.39, 95% CI: 1.06–1.82; P = 0.02) were significantly associated with higher risks of 90-day all-cause mortality in the total population. In both subgroups of patients aged 65–75 years (HR = 1.52, 95% CI: 1.04–2.21; P = 0.03) and ≥ 75 years (HR = 1.90, 95% CI: 1.23–2.94; P < 0.01), the presence of MetS was also associated with significantly higher risks of 90-day all-cause mortality.

Table 2 Multivariate Cox regression for exploring the association of MetS status with 90-day mortality
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The outcomes of patients with 0–1, 2, 3, and 4 of 4 metabolic criteria are portrayed in Fig. 3. With each metabolic syndrome criterion added from 0 to 1 to 2, 3, and 4 of 4 criteria, the 28-day (0–1 criteria: 16.8%; 2 criteria: 20.3%; 3 criteria: 24.9%; 4 criteria: 30.2%. P < 0.01) and 90-day all-cause mortality rates (0–1 criteria: 21.2%; 2 criteria: 25.1%; 3 criteria: 30.9%; 4 criteria: 36.4%. P < 0.01) increased significantly.

Fig. 3
figure 3

Additive associations of metabolic syndrome (MetS) individual criteria with (A) 28-day all-cause mortality rate and (B) 90-day all-cause mortality in the total population

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Discussion

ARDS is a common yet complex syndrome that develops in critically ill patients. Although ARDS can affect people of all ages, increasing age is a widely reported risk factor and is associated with increased mortality in ARDS patients. It may be explained by the decline in immune function, and age-related changes in structural components of the airway and vasculature [14]. The present study indicated in the total ARDS patients and its two subgroup (65–75 years and ≥ 75 years), presence of MetS was associated with a high risk of 28-day and 90-day all-cause mortality.

Two large cohort studies have been performed to evaluate the association of MetS and mortality in ARDS patients, but the conclusions are inconsistent. A prospective cohort study used data from 181 hospitals across 26 countries showed that metabolic syndrome was associated with increased risk of mortality (OR = 1.19, 95% CI: 1.08–1.31) in ARDS adult patients [15]. However, the other retrospective cohort study involving 4,288 ARDS patients indicated that MetS was associated with a lower risk of 28-day (OR = 0.70, 95% CI: 0.55–0.89) and 90-day mortality (OR = 0.75, 95% CI: 0.60–0.95) [12]. Our study supported MetS to be a risk factor for survival in ARDS patients as patients with MetS were not only at higher risk of mortality, but each additional metabolic syndrome criteria added was associated with greater risk of mortality in an additive fashion among patients with 0–1, 2, 3, or 4 metabolic syndrome criteria. Currently the mechanism for the association is not clear and remains to be fully elucidated by further studies.

Several investigators have reported age as an independent predictor of mortality in ARDS, which might be due to age-related decline in immune function and changes in structural components of the airway and vasculature. In a study based on US National Center for Health Statistics’ (NCHS) Multiple Cause of Death (MCOD) database, the average mortality rate was 19.51 per 100,000 for ARDS patients with 75–84 years, much higher than the mortality rate of 11.38 per 100,000 for those with 65–74 years [16]. Song et al. reported that the 100-day mortality rate was significantly higher (P = 0.0029) in those over 80 years old than in those under 40 years old, 40–60 years old and 60–80 years old [17]. Our study confirmed that advanced age is an independent risk factor for 90-day all-cause mortality. Moreover, in subgroups stratified by age, patients with MetS still have significantly higher risks of mortality.

In addition, scoring systems have been widely used to estimate prognosis in critically ill patients. SOFA score and APACHE II score are two identified independent predictors of increased mortality in ARDS patients [17, 18]. In line with these previous studies, this study also found that both scoring systems were significantly associated mortality. However, even SOFA score and APACHE II score were adjusted as confounding factors, MetS was still an independent prognostic factor for increased all-cause mortality.

There are several important limitations. First, due to the retrospective study design, some potential confounders such as socioeconomic factors were not collected. Furthermore, we were not able to assess consistency of adherence with lung protective ventilation strategies, an established high-quality intervention associated with improved survival. In addition, MetS status and its components are variable; they can change dynamically over time. This could have biased the results. Lastly, management of ARDS is not exactly the same between ICU and non-ICU settings. Although ICU admission was adjusted for in our multivariate Cox regression, it might still influence the outcomes. To eliminate this confounding factor, further studies to explore the association of MetS with mortality in ICU settings are required.

Conclusion

In conclusion, MetS was associated with a higher risk of 28-day and 90-day all-cause mortality in elderly patients with ARDS.

Data availability

No datasets were generated or analysed during the current study.

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Authors and Affiliations

  1. Intensive Care Unit (ICU), Shanghai Construction Group Hospital, No. 666, North Zhongshan Road Number One, Hongkou District, Shanghai, 200083, China

    Xiao Xu, Huajuan Xu, Ming Li, Shuying Yan & Huilin Chen

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Contributions

XX and HC conceived the study idea and designed the study; HX, ML, and SY acquired the data and performed the data analysis; XX drafted the manuscript; HC substantially revised the article. All authors agreed on the journal to which the article will be submitted, and agree to take responsibility and be accountable for the contents of the article.

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Correspondence to Huilin Chen.

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Ethics approval and informed consent

This study was approved by the Ethics Committee of Shanghai Construction Group Hospital (approval No. 2023036). All procedures involving human participants were performed by the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. As it is a retrospective study, informed consent was waived by the Ethic Committee of Shanghai Construction Group Hospital. All data were fully anonymized and kept confidentially.

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Xu, X., Xu, H., Li, M. et al. Metabolic syndrome is associated with mortality in elderly patients with acute respiratory distress syndrome. Diabetol Metab Syndr 16, 191 (2024). https://doi.org/10.1186/s13098-024-01420-x

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Diabetology & Metabolic Syndrome

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